proto oncogene proteins b raf

Summary

Summary: A raf kinase subclass found at high levels in neuronal tissue. The B-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.

Top Publications

  1. ncbi BRAF mutations in conjunctival melanoma
    Heather Gear
    Tennent Institute of Ophthalmology, Gartnavel General Hospital, Glasgow, Scotland, United Kingdom
    Invest Ophthalmol Vis Sci 45:2484-8. 2004
  2. ncbi Mutations of the BRAF gene in human cancer
    Helen Davies
    Cancer Genome Project, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK
    Nature 417:949-54. 2002
  3. ncbi Distinct sets of genetic alterations in melanoma
    John A Curtin
    Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143 0808, USA
    N Engl J Med 353:2135-47. 2005
  4. ncbi CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer
    Daniel J Weisenberger
    Department of Surgery, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90089 9176, USA
    Nat Genet 38:787-93. 2006
  5. ncbi Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF
    Paul T C Wan
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Cell 116:855-67. 2004
  6. ncbi Hyperactive Ras in developmental disorders and cancer
    Suzanne Schubbert
    Department of Pediatrics, University of California, 513 Parnassus Avenue, Room HSE 302, San Francisco, California 94143, USA
    Nat Rev Cancer 7:295-308. 2007
  7. ncbi BRAFE600-associated senescence-like cell cycle arrest of human naevi
    Chrysiis Michaloglou
    Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Nature 436:720-4. 2005
  8. pmc BRAF mutation predicts sensitivity to MEK inhibition
    David B Solit
    Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
    Nature 439:358-62. 2006
  9. ncbi BRAF and RAS mutations in human lung cancer and melanoma
    Marcia S Brose
    Department of Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Philadelphia 19104, USA
    Cancer Res 62:6997-7000. 2002
  10. pmc Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity
    James Tsai
    Plexxikon, Inc, 91 Bolivar Drive, Berkeley, CA 94710, USA
    Proc Natl Acad Sci U S A 105:3041-6. 2008

Detail Information

Publications256 found, 100 shown here

  1. ncbi BRAF mutations in conjunctival melanoma
    Heather Gear
    Tennent Institute of Ophthalmology, Gartnavel General Hospital, Glasgow, Scotland, United Kingdom
    Invest Ophthalmol Vis Sci 45:2484-8. 2004
    ..The purpose of this study was to determine whether the T1799A BRAF mutation found in cutaneous melanoma is also present in conjunctival melanoma...
  2. ncbi Mutations of the BRAF gene in human cancer
    Helen Davies
    Cancer Genome Project, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK
    Nature 417:949-54. 2002
    ..As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma...
  3. ncbi Distinct sets of genetic alterations in melanoma
    John A Curtin
    Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143 0808, USA
    N Engl J Med 353:2135-47. 2005
    ..We hypothesized that the clinical heterogeneity is explained by genetically distinct types of melanoma with different susceptibility to ultraviolet light...
  4. ncbi CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer
    Daniel J Weisenberger
    Department of Surgery, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90089 9176, USA
    Nat Genet 38:787-93. 2006
    ..Sporadic cases of mismatch repair deficiency occur almost exclusively as a consequence of CIMP-associated methylation of MLH1 . We propose a robust new marker panel to classify CIMP+ tumors...
  5. ncbi Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF
    Paul T C Wan
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Cell 116:855-67. 2004
    ..The high activity mutants signal to ERK by directly phosphorylating MEK, whereas the impaired activity mutants stimulate MEK by activating endogenous C-RAF, possibly via an allosteric or transphosphorylation mechanism...
  6. ncbi Hyperactive Ras in developmental disorders and cancer
    Suzanne Schubbert
    Department of Pediatrics, University of California, 513 Parnassus Avenue, Room HSE 302, San Francisco, California 94143, USA
    Nat Rev Cancer 7:295-308. 2007
    ..Here we will discuss the implications of germline mutations in the Ras-Raf-MEK-ERK pathway for understanding normal developmental processes and cancer pathogenesis...
  7. ncbi BRAFE600-associated senescence-like cell cycle arrest of human naevi
    Chrysiis Michaloglou
    Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Nature 436:720-4. 2005
    ..Thus, both in vitro and in vivo, BRAF(V600E)-expressing melanocytes display classical hallmarks of senescence, suggesting that oncogene-induced senescence represents a genuine protective physiological process...
  8. pmc BRAF mutation predicts sensitivity to MEK inhibition
    David B Solit
    Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
    Nature 439:358-62. 2006
    ..These data suggest an exquisite dependency on MEK activity in BRAF mutant tumours, and offer a rational therapeutic strategy for this genetically defined tumour subtype...
  9. ncbi BRAF and RAS mutations in human lung cancer and melanoma
    Marcia S Brose
    Department of Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Philadelphia 19104, USA
    Cancer Res 62:6997-7000. 2002
    ..Although uncommon, BRAF mutations in human lung cancers may identify a subset of tumors sensitive to targeted therapy...
  10. pmc Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity
    James Tsai
    Plexxikon, Inc, 91 Bolivar Drive, Berkeley, CA 94710, USA
    Proc Natl Acad Sci U S A 105:3041-6. 2008
    ....
  11. pmc CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer
    Shuji Ogino
    Center for Molecular Oncologic Pathology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115 USA
    Gut 58:90-6. 2009
    ..The independent effect of CIMP, MSI and BRAF mutation on prognosis remains uncertain...
  12. pmc BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum
    T Kambara
    Conjoint Gastroenterology Laboratory, Royal Brisbane and Women s Hospital Research Foundation and Queensland Institute of Medical Research, Brisbane 4029, Australia
    Gut 53:1137-44. 2004
    ..However, the distribution of BRAF mutations in MSI-H cancers remains to be clarified with respect to precursor lesions and the CpG island methylator phenotype (CIMP)...
  13. ncbi Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers
    Wade S Samowitz
    Department of Pathology, University of Utah Health Sciences Center, Salt Lake City 84132, USA
    Cancer Res 65:6063-9. 2005
    ....
  14. ncbi The RAF proteins take centre stage
    Claudia Wellbrock
    Signal Transduction Team, Cancer Research UK Centre of Cell and Molecular Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    Nat Rev Mol Cell Biol 5:875-85. 2004
    ....
  15. ncbi A dimerization-dependent mechanism drives RAF catalytic activation
    Thanashan Rajakulendran
    Centre for Systems Biology, Samuel Lunenfeld Research Institute, Toronto, Ontario M5G 1X5, Canada
    Nature 461:542-5. 2009
    ..Together, our data identify the side-to-side dimer interface of RAF as a potential therapeutic target for intervention in BRAF-dependent tumorigenesis...
  16. ncbi BRAF mutation in thyroid cancer
    M Xing
    Division of Endocrinology and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, 1830 E Monument St Suite 333 Baltimore, MD 21287, USA
    Endocr Relat Cancer 12:245-62. 2005
    ..This newly discovered BRAF mutation may prove to have an important impact on thyroid cancer in the clinic...
  17. ncbi BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas
    Marina N Nikiforova
    Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio 45267, USA
    J Clin Endocrinol Metab 88:5399-404. 2003
    ..They are associated with distinct phenotypical and biological properties of papillary carcinomas and may participate in progression to poorly differentiated and anaplastic carcinomas...
  18. pmc A new mouse model to explore the initiation, progression, and therapy of BRAFV600E-induced lung tumors
    David Dankort
    Cancer Research Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco Comprehensive Cancer Center, California 94143, USA
    Genes Dev 21:379-84. 2007
    ..Consistent with Ink4a/Arf and TP53 tumor suppressor function, BRaf(VE) expression combined with mutation of either locus led to cancer progression...
  19. ncbi Hypermethylator phenotype in sporadic colon cancer: study on a population-based series of 582 cases
    Ludovic Barault
    Service d Anatomie Pathologique, Institut National de la Sante et de la Recherche Medicale, Universite de Bourgogne, Dijon, France
    Cancer Res 68:8541-6. 2008
    ..Our results show the interest of defining three subgroups of patients according to their methylation status (No-CIMP/CIMP-Low/CIMP-High). Methylation is an independent prognostic factor in MSS colon cancer...
  20. ncbi Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer
    Federica Di Nicolantonio
    Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino, Medical School, Candiolo, Torino, Italy
    J Clin Oncol 26:5705-12. 2008
    ..Double-hit therapies aimed at simultaneous inhibition of epidermal growth factor receptor and BRAF warrant exploration in CRC patients carrying the V600E oncogenic mutation...
  21. pmc Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF
    Sonja J Heidorn
    The Institute of Cancer Research, Signal Transduction Team, Section of Cell and Molecular Biology, 237 Fulham Road, London SW3 6JB, UK
    Cell 140:209-21. 2010
    ....
  22. pmc Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma
    Clara Montagut
    Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts, USA
    Cancer Res 68:4853-61. 2008
    ..Geldanamycin effectively promotes the degradation of CRAF, thereby revealing a potential therapeutic strategy to overcome resistance to RAF inhibition in a subset of BRAF mutant tumors...
  23. ncbi NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing
    Esther Edlundh-Rose
    Department of Gene Technology, School of Biotechnology, Royal Institute of Technology KTH, AlbaNova University Center, Stockholm, Sweden
    Melanoma Res 16:471-8. 2006
    ..7). In conclusion, the separate genotypes were associated with differences in several key clinical and pathological parameters, indicating differences in the biology of melanoma tumours with different proto-oncogene mutations...
  24. pmc Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma
    Hensin Tsao
    Wellman Laboratories, Department of Dermatology, Massachusetts General Hospital Melanoma Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Invest Dermatol 122:337-41. 2004
    ..These findings suggest the existence of possible cooperation between BRAF activation and PTEN loss in melanoma development...
  25. ncbi Mutant V599EB-Raf regulates growth and vascular development of malignant melanoma tumors
    Arati Sharma
    Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey 17033, USA
    Cancer Res 65:2412-21. 2005
    ..Thus, these studies identify the mechanistic underpinnings by which mutant (V599E)B-RAF promotes melanoma development and show the effectiveness of targeting this protein to inhibit melanoma tumor growth...
  26. ncbi BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer
    Mingzhao Xing
    Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287, USA
    J Clin Endocrinol Metab 90:6373-9. 2005
    ..Use of BRAF mutation in papillary thyroid cancer (PTC) has the potential to improve risk stratification of this cancer...
  27. ncbi Metastatic potential of melanomas defined by specific gene expression profiles with no BRAF signature
    Keith S Hoek
    Department of Dermatology, University Hospital of Zurich, 8091 Zurich, Switzerland
    Pigment Cell Res 19:290-302. 2006
    ....
  28. ncbi Determinants of BRAF mutations in primary melanomas
    Janet L Maldonado
    Department of Dermatology, University of California, San Francisco, San Francisco, CA 94115, USA
    J Natl Cancer Inst 95:1878-90. 2003
    ..The high mutation frequency in melanomas arising on intermittently sun-exposed skin suggests a complex causative role of such exposure that mandates further evaluation...
  29. ncbi BRAF mutations characterize colon but not gastric cancer with mismatch repair deficiency
    Carla Oliveira
    Instituto de Patologia e Imunologia Molecular da Universidade do Porto IPATIMUP, Porto 4200 465, Portugal
    Oncogene 22:9192-6. 2003
    ..Accordingly, our results show evidences that BRAF mutations characterize colon but not gastric tumors with MMR deficiency and are not involved in the tumorigenesis of gastric cancer of the mutator phenotype pathway...
  30. ncbi BRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas
    Tsun L Chan
    Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong
    Cancer Res 63:4878-81. 2003
    ..The high incidence of BRAF mutations in HPs and SAs is consistent with the notion that the group of colorectal cancers carrying BRAF mutations may harbor most that have progressed through the HP-SA-carcinoma pathway...
  31. ncbi Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid: a meta-analysis
    Ju Han Lee
    Department of Pathology, Bioinformatics Interest Group, Korea University Ansan Hospital, Ansan, Republic of Korea
    Cancer 110:38-46. 2007
    ..To address this controversy, the frequency of the BRAF mutation and the associations between BRAF mutation and clinicopathologic parameters in PTC were evaluated by meta-analysis...
  32. pmc Prognostic significance of defective mismatch repair and BRAF V600E in patients with colon cancer
    Amy J French
    Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street Southwest, 920 Hilton Building, Rochester, MN 55905, USA
    Clin Cancer Res 14:3408-15. 2008
    ..Although the presence of dMMR seems to be a favorable prognostic marker, data suggest that these patients do not respond as well to adjuvant chemotherapy...
  33. ncbi Missense mutations of the BRAF gene in human lung adenocarcinoma
    Katsuhiko Naoki
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 62:7001-3. 2002
    ..These specimens belong to the same adenocarcinoma subgroup as defined by clustering of gene expression data. BRAF may provide a target for anticancer chemotherapy in a subset of lung adenocarcinoma patients...
  34. pmc BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing
    E Domingo
    Centre d Investigacions en Bioquimica i Biologia Molecular CIBBIM, Hospital Universitari Vall d Hebron, Passeig Vall d Hebron 119 129, Barcelona 08035, Spain
    J Med Genet 41:664-8. 2004
    ....
  35. pmc Comprehensive biostatistical analysis of CpG island methylator phenotype in colorectal cancer using a large population-based sample
    Katsuhiko Nosho
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
    PLoS ONE 3:e3698. 2008
    ..In stratified analyses, the relations of CIMP-high with poor differentiation, KRAS mutation and LINE-1 hypomethylation significantly differed according to MSI status...
  36. ncbi Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization
    Mathew J Garnett
    Signal Transduction Team, The Institute of Cancer Research, Cancer Research UK Centre of Cell and Molecular Biology, London
    Mol Cell 20:963-9. 2005
    ..Thus, we have identified a B-RAF-C-RAF-MEK-ERK cascade that signals not only in cancer but also in normal cells...
  37. ncbi Comparison of microsatellite instability, CpG island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distinct colorectal carcinoma end points
    Michael J O'Brien
    Department of Pathology, Boston University Medical Center, Boston, MA 02118, USA
    Am J Surg Pathol 30:1491-501. 2006
    ....
  38. ncbi Mutation analysis of the BRAF, ARAF and RAF-1 genes in human colorectal adenocarcinomas
    Karin Fransen
    Division of Cell Biology, Floor 9, Department of Biomedicine and Surgery, Faculty of Health Sciences, Linkoping University, SE 581 85 Linkoping, Sweden
    Carcinogenesis 25:527-33. 2004
    ..Collectively, our results provide support for the idea that activation of the MAP kinase pathway, especially via BRAF and KRAS mutations, is of critical importance for the development of colorectal cancer...
  39. ncbi BRAF and KRAS Mutations in hyperplastic polyps and serrated adenomas of the colorectum: relationship to histology and CpG island methylation status
    Shi Yang
    Department of Pathology, Boston Medical Center, Boston, MA 02118, USA
    Am J Surg Pathol 28:1452-9. 2004
    ..In contrast, the association of higher levels of CpG island methylation with more advanced histologic changes suggests that CpG island methylation plays a role in serrated polyp progression toward colorectal carcinoma...
  40. ncbi Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers
    Hiroyuki Namba
    Department of Molecular Medicine, Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Sakamoto, Japan
    J Clin Endocrinol Metab 88:4393-7. 2003
    ..033) and clinical stage (P = 0.049). Our results indicate that activating mutation of BRAF gene could be a potentially useful marker of prognosis of patients with advanced thyroid cancers...
  41. pmc PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer
    Shuji Ogino
    Department of Medical Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Harvard Medical School, 44 Binney St, Room JF 215C, Boston, MA 02115 USA
    J Clin Oncol 27:1477-84. 2009
    ..PIK3CA mutation and subsequent activation of the AKT pathway play an important role in colorectal carcinogenesis. However, little is known about the prognostic role of PIK3CA mutation in colon cancer...
  42. ncbi Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome
    Tetsuya Niihori
    Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan
    Nat Genet 38:294-6. 2006
    ....
  43. ncbi A new BRAF gene mutation detected in a case of a solid variant of papillary thyroid carcinoma
    Vitor Trovisco
    Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
    Hum Pathol 36:694-7. 2005
    ..The genetic study of more cases of the solid variant of PTC is necessary to find whether there exists a significant association between the occurrence of BRAF(VK600-1E) and such PTC histotype...
  44. pmc Braf(V600E) cooperates with Pten loss to induce metastatic melanoma
    David Dankort
    Cancer Research Institute and Department of Cell and Molecular Pharmacology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, USA
    Nat Genet 41:544-52. 2009
    ..These mice, engineered with a common genetic profile to human melanoma, provide a system to study melanoma's cardinal feature of metastasis and for preclinical evaluation of agents designed to prevent or treat metastatic disease...
  45. pmc Combinatorial activities of Akt and B-Raf/Erk signaling in a mouse model of androgen-independent prostate cancer
    Hui Gao
    Center for Advanced Biotechnology and Medicine, Cancer Institute of New Jersey, and Department of Medicine, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, NJ 08854, USA
    Proc Natl Acad Sci U S A 103:14477-82. 2006
    ..We propose that androgen independence emerges by means of epithelial-stromal competition, in which activation of Akt and Erk promotes AR activity in the prostate epithelium while counteracting antagonistic effects of the stroma...
  46. ncbi Association of smoking, CpG island methylator phenotype, and V600E BRAF mutations in colon cancer
    Wade S Samowitz
    Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT 84132, USA
    J Natl Cancer Inst 98:1731-8. 2006
    ..We investigated whether the association between smoking and all colon cancers could be explained through induction of CIMP and/or BRAF mutations...
  47. pmc Genetic and epigenetic changes in primary metastatic and nonmetastatic colorectal cancer
    E Miranda
    Molecular Genetics Laboratory, Istituto Clinico Humanitas, University of Milan, Via Manzoni 56, Rozzano, Milano 20089, Italy
    Br J Cancer 95:1101-7. 2006
    ....
  48. pmc Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas
    Keiran S M Smalley
    The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
    Mol Cancer Ther 7:2876-83. 2008
    ....
  49. ncbi Toward a molecular classification of melanoma
    Leslie A Fecher
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, USA
    J Clin Oncol 25:1606-20. 2007
    ..We eagerly anticipate rationally designed melanoma therapies based on such a classification scheme and the associated improvements in patient outcomes...
  50. ncbi BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma
    Jianli Dong
    Department of Pathology, Mount Sinai School of Medicine, New York, New York 10029, USA
    Cancer Res 63:3883-5. 2003
    ....
  51. ncbi Human malignant melanoma: detection of BRAF- and c-kit-activating mutations by high-resolution amplicon melting analysis
    Carlynn Willmore-Payne
    Department of Pathology, University of Utah, Salt Lake City, 84108, USA
    Hum Pathol 36:486-93. 2005
    ....
  52. ncbi High prevalence of BRAF gene mutation in papillary thyroid carcinomas and thyroid tumor cell lines
    Xiulong Xu
    Department of General Surgery, Rush Presbyterian St Luke s Medical Center, 1653 West Congress Parkway, Chicago, IL 60612, USA
    Cancer Res 63:4561-7. 2003
    ..These observations suggest that mutated BRAF gene may cooperate with RET/PTC to induce the oncogenesis of PTC...
  53. pmc The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells
    Rosa Marina Melillo
    Istituto di Endocrinologia ed Oncologia Sperimentale del CNR G Salvatore, Dipartimento di Biologia e Patologia Cellulare e Molecolare, University Federico II, Naples, Italy
    J Clin Invest 115:1068-81. 2005
    ..Thus, motile and mitogenic properties are intrinsic to transformed thyroid cells and are governed by an epistatic oncogenic signaling cascade...
  54. ncbi BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma
    E Elizabeth Patton
    Howard Hughes Medical Institute, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
    Curr Biol 15:249-54. 2005
    ....
  55. ncbi BRAF V600E disrupts AZD6244-induced abrogation of negative feedback pathways between extracellular signal-regulated kinase and Raf proteins
    Bret B Friday
    Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA
    Cancer Res 68:6145-53. 2008
    ..These data suggest an approach to identifying cells that may be sensitive to AZD6244 and other MEK inhibitors...
  56. pmc BRAFV600E mutation is associated with preferential sensitivity to mitogen-activated protein kinase kinase inhibition in thyroid cancer cell lines
    Rebecca Leboeuf
    Department of Medicine and Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    J Clin Endocrinol Metab 93:2194-201. 2008
    ..Although the signal output common to these oncoproteins is ERK, a recent report showed that only BRAF mutations consistently predicted responsiveness to MAPK kinase (MEK) inhibitors...
  57. ncbi Mutant B-RAF mediates resistance to anoikis via Bad and Bim
    K Boisvert-Adamo
    Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, USA
    Oncogene 27:3301-12. 2008
    ..Depletion of Bim together with Bad has an additive effect on protecting B-RAF knockdown cells from anoikis. Together, our data show that Bad and Bim are major B-RAF responsive proteins regulating apoptosis in melanoma cells...
  58. ncbi BRAF mutations in papillary carcinomas of the thyroid
    Toshihiko Fukushima
    Department of Surgery, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960 1295, Japan
    Oncogene 22:6455-7. 2003
    ..No mutations were found in KRAS or HRAS. Our results suggest that BRAF mutations may play a critical role in the carcinogenesis of papillary carcinoma of the thyroid...
  59. ncbi Oncogenes in melanoma
    David Polsky
    Department of Dermatology, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA
    Oncogene 22:3087-91. 2003
    ..We provide a general overview of the mechanisms of oncogene activation and the functions of oncogenes. Lastly, we review oncogenic events in melanoma...
  60. ncbi BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study
    Rossella Elisei
    Department of Endocrinology, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy
    J Clin Endocrinol Metab 93:3943-9. 2008
    ..In this study we verified the prognostic value of the BRAF(V600E) mutation in PTC patients with a long-term follow-up...
  61. ncbi Tumor necrosis factor-alpha blocks apoptosis in melanoma cells when BRAF signaling is inhibited
    Vanessa C Gray-Schopfer
    Signal Transduction Team, Cancer Research UK Centre of Cell and Molecular Biology, The Institute of Cancer Research, 237 Fulham Road, London, United Kingdom
    Cancer Res 67:122-9. 2007
    ..These findings suggest that drugs that target the BRAF/MEK pathway could be combined with agents that target TNF-alpha and/or NF-kappaB signaling to provide exciting new therapeutic opportunities for the treatment of melanoma...
  62. pmc PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab
    Minaxi Jhawer
    Department of Oncology, Montefiore Medical Center, Albert Einstein Cancer Center, Bronx, NY 10467, USA
    Cancer Res 68:1953-61. 2008
    ..A priori screening of colon tumors for PTEN expression status and PIK3CA and Ras/BRAF mutation status could help stratify patients likely to benefit from this therapy...
  63. ncbi Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome
    Pablo Rodriguez-Viciana
    Comprehensive Cancer Center and Cancer Research Institute, University of California, San Francisco, CA 94115, USA
    Science 311:1287-90. 2006
    ..Our findings highlight the involvement of the MAPK pathway in human development and will provide a molecular diagnosis of CFC syndrome...
  64. pmc Expression of endogenous oncogenic V600EB-raf induces proliferation and developmental defects in mice and transformation of primary fibroblasts
    Kathryn Mercer
    Department of Biochemistry, University of Leicester, UK
    Cancer Res 65:11493-500. 2005
    ..Thus, (V600E)B-Raf is able to induce several hallmarks of transformation in some primary mouse cells without evidence for the involvement of a cooperating oncogene or tumor suppressor gene...
  65. ncbi BRAF mutations are associated with some histological types of papillary thyroid carcinoma
    Vitor Trovisco
    IPATIMUP Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
    J Pathol 202:247-51. 2004
    ....
  66. pmc Targeting the mitogen-activated protein kinase pathway: physiological feedback and drug response
    Christine A Pratilas
    Department of Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Clin Cancer Res 16:3329-34. 2010
    ....
  67. pmc Uncoupling of the LKB1-AMPKalpha energy sensor pathway by growth factors and oncogenic BRAF
    Rosaura Esteve-Puig
    Animal Models and Cancer Laboratory, Medical Oncology Research Program, Vall d Hebron Research Institute VHIO, Vall d Hebron Hospital, Barcelona, Spain
    PLoS ONE 4:e4771. 2009
    ..Additionally, LKB1(Ser428) becomes phosphorylated in a RAS-Erk1/2-p90(RSK) pathway dependent manner. However, the connection between the RAS pathway and LKB1 is mostly unknown...
  68. ncbi BRAF mutations in metastatic melanoma: a possible association with clinical outcome
    Rajiv Kumar
    Department of Biosciences, Karolinska Institute, Novum, 141 57 Huddinge, Sweden
    Clin Cancer Res 9:3362-8. 2003
    ..Recently, activating mutations in the BRAF gene, were reported in a large proportion of melanomas. We have studied mutations in the BRAF gene and their association with clinical parameters...
  69. ncbi Guilty as charged: B-RAF is a human oncogene
    Mathew J Garnett
    Signal Transduction Team, Cancer Research UK Centre for Cell and Molecular Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, United Kingdom
    Cancer Cell 6:313-9. 2004
    ..Here we review the rapid progress made in our understanding of B-RAF as an oncogene and of its role in cancer...
  70. pmc Cyclic AMP inhibits the proliferation of thyroid carcinoma cell lines through regulation of CDK4 phosphorylation
    Ana Sofia Rocha
    Institute of Interdisciplinary Research IRIBHM, Universite Libre de Bruxelles, Campus Erasme, B 1070 Brussels, Belgium
    Mol Biol Cell 19:4814-25. 2008
    ....
  71. pmc Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers
    Alex A Adjei
    Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
    J Clin Oncol 26:2139-46. 2008
    ..To assess the tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of the mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancer...
  72. pmc Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells
    J Liu
    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 6046, USA
    Oncogene 26:1954-8. 2007
    ..Taken together, these data support a model in which mutational activation of BRAF in human melanomas contributes to constitutive induction of NF-kappaB activity and to increased survival of melanoma cells...
  73. pmc Targeting V600EB-Raf and Akt3 using nanoliposomal-small interfering RNA inhibits cutaneous melanocytic lesion development
    Melissa A Tran
    Department of Pharmacology, The Pennsylvania State University, Hershey, Pennsylvania 17033, USA
    Cancer Res 68:7638-49. 2008
    ..Thus, cationic nanoliposomes loaded with siRNA targeting (V600E)B-Raf and Akt3 provide an effective approach for targeted inhibition of early or invasive cutaneous melanomas...
  74. ncbi Oncogenic Braf induces melanocyte senescence and melanoma in mice
    Nathalie Dhomen
    Signal Transduction Team, Cancer Research UK Centre for Cell and Molecular Biology, The Institute of Cancer Research, London, UK
    Cancer Cell 15:294-303. 2009
    ..Thus, we have developed a mouse model of melanoma driven by Braf(V600E) expressed at physiological levels that reflects the genetics and pathology of the human disease...
  75. ncbi Inactivation of the mitogen-activated protein kinase pathway as a potential target-based therapy in ovarian serous tumors with KRAS or BRAF mutations
    Gudrun Pohl
    Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA
    Cancer Res 65:1994-2000. 2005
    ....
  76. ncbi Mutation of B-Raf in human choroidal melanoma cells mediates cell proliferation and transformation through the MEK/ERK pathway
    Armelle Calipel
    Institut Biomedical des Cordeliers, INSERM U450, 15 rue de l Ecole de Medecine, 75006 Paris, France
    J Biol Chem 278:42409-18. 2003
    ..Our results pinpoint this pathway as an important component in choroidal melanoma cell lines...
  77. pmc Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis
    T Eisen
    Royal Marsden Hospital, Downs Road, Surrey SMT 5PT, UK
    Br J Cancer 95:581-6. 2006
    ..i.d.). Ongoing trials in advanced melanoma are evaluating sorafenib combination therapies...
  78. ncbi High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma
    Edna T Kimura
    Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA
    Cancer Res 63:1454-7. 2003
    ..Because these signaling proteins function along the same pathway in thyroid cells, this represents a unique paradigm of human tumorigenesis through mutation of three signaling effectors lying in tandem...
  79. ncbi Molecular differences between sporadic serrated and conventional colorectal adenomas
    Kazuo Konishi
    Second Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan
    Clin Cancer Res 10:3082-90. 2004
    ..The purpose is to compare the molecular characteristics of serrated adenomas (SAs) with those of conventional adenomas (CADs) and hyperplastic polyps (HPs)...
  80. pmc Akt3 and mutant V600E B-Raf cooperate to promote early melanoma development
    Mitchell Cheung
    Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Cancer Res 68:3429-39. 2008
    ....
  81. ncbi Activation of ERK1/2 occurs independently of KRAS or BRAF status in endometrial cancer and is associated with favorable prognosis
    Yasunari Mizumoto
    Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kanazawa University, 13 1, Takaramachi, Kanazawa, Ishikawa 920 8641, Japan
    Cancer Sci 98:652-8. 2007
    ..047). These findings suggest that ERK activation occurs in a KRAS- and BRAF-independent manner in endometrial cancer, and is associated with favorable prognosis...
  82. ncbi Absence of BRAF and NRAS mutations in uveal melanoma
    Frank Cruz
    Oregon Health and Science University OHSU Cancer Institute, Department of Pathology, OHSU and Portland Veterans Affairs Medical Center, Portland, Oregon 97239, USA
    Cancer Res 63:5761-6. 2003
    ..No NRAS exon 1 mutations were detected in either type of melanoma. We conclude that UMs arise independent of oncogenic BRAF and NRAS mutations, an observation that may have implications for therapies targeted to the NRAS-BRAF pathway...
  83. ncbi High glucose stimulates synthesis of fibronectin via a novel protein kinase C, Rap1b, and B-Raf signaling pathway
    Sun Lin
    Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611, USA
    J Biol Chem 277:41725-35. 2002
    ..This effect appears to be PKC-dependent and PDGF-independent, but involves B-Raf, suggesting a novel PKC-Rap1b-B-Raf pathway responsible for HG-induced increased mesangial matrix synthesis, a hallmark of diabetic nephropathy...
  84. ncbi Influence of the BRAF V600E mutation on expression of vascular endothelial growth factor in papillary thyroid cancer
    Young Suk Jo
    Division of Endocrinology, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 301 721, Korea
    J Clin Endocrinol Metab 91:3667-70. 2006
    ..The BRAF mutation may influence the expression patterns of molecular markers that are related to the development and progression of thyroid cancer...
  85. pmc Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer
    Raffaele Ciampi
    Department of Pathology and Laboratory Medicine and Division of Endocrinology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267 0529, USA
    J Clin Invest 115:94-101. 2005
    ....
  86. ncbi The methylator phenotype in microsatellite stable colorectal cancers is characterized by a distinct gene expression profile
    M Ferracin
    Dipartimento di Medicina Sperimentale e Diagnostica, Universita di Ferrara, Via Luigi Borsari 46, 44100 Ferrara, Italy
    J Pathol 214:594-602. 2008
    ..Microarray analysis revealed that CIMP+ tumours are characterized by a unique expression profile, a result that confirms that CIMP+ tumours represent a truly distinct molecular class within MSS colorectal cancers...
  87. ncbi Promoter methylation of the mutated in colorectal cancer gene is a frequent early event in colorectal cancer
    M R J Kohonen-Corish
    Cancer Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
    Oncogene 26:4435-41. 2007
    ..Furthermore, MCC methylation is significantly associated with a distinct spectrum of precursor lesions, which are suggested to give rise to cancers via the serrated neoplasia pathway...
  88. ncbi High prevalence of sessile serrated adenomas with BRAF mutations: a prospective study of patients undergoing colonoscopy
    Kevin J Spring
    Conjoint Gastroenterology Laboratory, Queensland Institute of Medical Research, Herston, Brisbane, Australia
    Gastroenterology 131:1400-7. 2006
    ..This prospective study examined the prevalence of sessile serrated adenomas and determined the incidence of BRAF and K-ras mutations in different types of polyps...
  89. ncbi Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer
    Milo Frattini
    Department of Pathology, Experimental Molecular Pathology, Istituto Nazionale Tumori, Milan, Italy
    Oncogene 23:7436-40. 2004
    ..However, a supervised analysis of the obtained data identified a subset of genes differentially expressed in tumors carrying BRAF mutation or RTK rearrangement...
  90. pmc PIK3CA mutation in colorectal cancer: relationship with genetic and epigenetic alterations
    Katsuhiko Nosho
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Neoplasia 10:534-41. 2008
    ..In addition, Pyrosequencing is useful in detecting PIK3CA mutation in archival paraffin tumor tissue. PIK3CA mutational data further emphasize heterogeneity of colorectal cancer at the molecular level...
  91. pmc Oncogenic B-RAF negatively regulates the tumor suppressor LKB1 to promote melanoma cell proliferation
    Bin Zheng
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    Mol Cell 33:237-47. 2009
    ..Our findings provide a molecular linkage between the LKB1-AMPK and the RAF-MEK-ERK pathways and suggest that suppression of LKB1 function by B-RAF V600E plays an important role in B-RAF V600E-driven tumorigenesis...
  92. pmc Analysis of the association between CIMP and BRAF in colorectal cancer by DNA methylation profiling
    Toshinori Hinoue
    USC Epigenome Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
    PLoS ONE 4:e8357. 2009
    ..Our data will be useful for future investigations toward understanding CIMP in colorectal cancer and gaining insights into the role of aberrant DNA hypermethylation in colorectal tumorigenesis...
  93. pmc PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells
    Ruth Halaban
    Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA
    Pigment Cell Melanoma Res 23:190-200. 2010
    ..The results suggest that the drug can confer an advantage to BRAF(WT) primary and metastatic tumor cells in vivo and provide markers for monitoring clinical responses...
  94. ncbi Effective inhibition of cell growth and invasion of melanoma by combined suppression of BRAF (V599E) and Skp2 with lentiviral RNAi
    Hidetoshi Sumimoto
    Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan
    Int J Cancer 118:472-6. 2006
    ..Our results suggest that gene therapy against melanoma with the enhanced MAPK and ubiquitin-proteasomal pathways could be a specific and effective therapeutic strategy for cancers...
  95. pmc V600E B-Raf requires the Hsp90 chaperone for stability and is degraded in response to Hsp90 inhibitors
    O M Grbovic
    Program in Molecular Pharmacology and Chemistry and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 103:57-62. 2006
    ..Hsp90 inhibition represents a therapeutic strategy for the treatment of melanoma...
  96. ncbi Lack of BRAF mutations in uveal melanoma
    Donata Rimoldi
    Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Switzerland
    Cancer Res 63:5712-5. 2003
    ....
  97. ncbi Conditional activation of RET/PTC3 and BRAFV600E in thyroid cells is associated with gene expression profiles that predict a preferential role of BRAF in extracellular matrix remodeling
    Cleo Mesa
    Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267, USA
    Cancer Res 66:6521-9. 2006
    ..The preferential induction of MMPs by BRAF could explain in part the more invasive behavior of thyroid cancers with BRAF mutations...
  98. ncbi Mutations of BRAF and KRAS precede the development of ovarian serous borderline tumors
    Chung Liang Ho
    Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA
    Cancer Res 64:6915-8. 2004
    ..Our findings provide cogent evidence that mutations of BRAF and KRAS occur in the epithelium of cystadenomas adjacent to SBTs and strongly suggest that they are very early events in tumorigenesis, preceding the development of SBT...
  99. ncbi BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC
    Paula Soares
    Institute of Molecular Pathology and Immunology of the University of Porto, IPATIMUP, Rua Roberto Frias s n, 4200 465 Porto, Portugal
    Oncogene 22:4578-80. 2003
    ..BRAF(V599E) may represent an alternative pathway to oncogenic MAPK activation in PTCs without RET/PTC activation...
  100. pmc Duplication of 7q34 in pediatric low-grade astrocytomas detected by high-density single-nucleotide polymorphism-based genotype arrays results in a novel BRAF fusion gene
    Angela J Sievert
    Division of Oncology, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Brain Pathol 19:449-58. 2009
    ..Further studies are required to determine the role of this fusion gene in downstream MAPK signaling and its role in development of pediatric low-grade astrocytomas...
  101. ncbi Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885
    Alastair J King
    Department of Oncology, MMPD CEDD, GlaxoSmithKline, Collegeville, Pennsylvania 19426, USA
    Cancer Res 66:11100-5. 2006
    ....

Research Grants42

  1. SBIR 2009 TOPIC 255- TITLE: PYRIDINOPYRIMIDE ANALOGS
    Weibo Wang; Fiscal Year: 2009
    ..The proposed analogs will be synthesized and tested against B-Raf kinases and cancer cell lines. Desirable compounds will be moved quickly to preclinical and clinical studies. ..
  2. RAS/BRAF Melanoma Mutations: Precursors, Risk, Prognosis
    Nancy Thomas; Fiscal Year: 2004
    ..This study is also expected to lead to identification of new chemotherapeutic targets and more efficient testing of inhibitors for NRAS and BRAF signaling, which have recently been developed. ..
  3. Melanoma NRAS/BRAF Mutations: A Population-Based Study
    Nancy Thomas; Fiscal Year: 2007
    ..This study is also expected to lead to identification of new hemotherapeutic targets and more efficient testing of inhibitors for NRAS and BRAF signaling, which have recently been developed. ..
  4. Pathogenesis of Ovarian Serous Borderline Tumors
    Robert J Kurman; Fiscal Year: 2010
    ..This will refine diagnostic and prognostic markers of advanced stage tumors. These results will be expected to have a significant impact on the clinical management of patients with this disease. ..
  5. MECHANISMS OF TRANSFORMATION OF HEMATOPOIETIC CELLS
    JAMES MC CUBREY; Fiscal Year: 2001
    ..An understanding of how these signal transduction and apoptotic pathways impinge upon one another will further our comprehension of the consequences of abnormal oncogene activation and tumor progression. ..
  6. Ras/Raf & PI3K/Akt Induced Breast Cancer Drug Resistance
    JAMES MC CUBREY; Fiscal Year: 2007
    ..Throughthese studies,moreinformationwillbe availableto treatbreast andothercancerpatientswithcombinationsof drugs,whichinhibitsignaltransductionand anti-apoptoticpathwaysleadingtodrug resistance. ..
  7. Regulation of Mitochondrial Fission/Fusion by PP2A and PKA in Neurons
    Stefan Strack; Fiscal Year: 2009
    ..Our studies may ultimately lead to better therapies for stroke and neurodegenerative disorders. ..
  8. 1st Costello Syndrome Symposium
    KATHERINE RAUEN; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  9. Extracellular matrix and protease markers of malignant thyroid neoplasm
    Electron Kebebew; Fiscal Year: 2007
    ..We will use these results to design a multicenter clinical trial evaluating the diagnostic and prognostic value of ECM1 and TMPRSS4 expression in patients with thyroid neoplasm. [unreadable] [unreadable] [unreadable]..
  10. MEK singaling in sarcoma growth and vascularization.
    NICHOLAS DUESBERY; Fiscal Year: 2007
    ..i ..
  11. Validating microRNA Analysis in Human Postmortem Brain
    Yogesh Dwivedi; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  12. Senescence and Longevity Modulating Genes, WRN and BLM
    Judith Campisi; Fiscal Year: 2008
    ..Our studies will provide important insights into how WRN and BLM postpone the development of aging phenotypes and the development of cancer in humans. ..
  13. Role of WRN in Longevity Assurance
    Judith Campisi; Fiscal Year: 2008
    ..abstract_text> ..
  14. Combination Strategies for Angiogenesis Inhibition
    Keith Flaherty; Fiscal Year: 2008
    ..He is a recognized leader in the field of investigational therapies, has a record of mentoring successful clinical researchers, and is committed to Dr. Flaherty's training. ..
  15. Regulatory subunits of PP2A in neuronal function
    Stefan Strack; Fiscal Year: 2011
    ..These studies are significant in that they advance our understanding of the critical regulatory enzyme PP2A with the ultimate goal of better therapies for several neurodegenerative disorders. ..
  16. FUNCTIONAL ANALYSIS OF THE PTEN TUMOR SUPPRESSOR PROTEIN
    Levi Garraway; Fiscal Year: 2009
    ..Based on this data we propose in specific aims 2 and 3: 2. To generate antibody reagents that selectively recognizes unphosphorylated PTEN. 3. To purify and identify proteins in the PTEN associated complex (PAC). ..
  17. MAP Kinase and AKT Signaling in Congestive Heart Failure
    ANTHONY MUSLIN; Fiscal Year: 2009
    ..Our findings will help to identify specific signaling mechanisms involved in the regulation of cardiac myocyte growth and metabolism. ..
  18. Genetics of Serrated Neoplasia
    Joanne Young; Fiscal Year: 2009
    ..In this proposal, we will explore the notion that the predisposition to form hyperplastic polyps may be inherited in families. ..
  19. Mutant mouse models of exocrine pancreatic cancer
    DAVID TUVESON; Fiscal Year: 2008
    ..Information gained from this murine model should facilitate further understanding of human pancreatic cancer. ..
  20. G2 CHECKPOINT FUNCTION IN HUMAN FIBROBLASTS
    William Kaufmann; Fiscal Year: 2007
    ..following DNA replication? Does ATR sends a signal through BRCA1 to inhibit Plkl when chromatid catenations are sensed? Is defective decatenation checkpoint function associated with genetic instability in cancer? ..
  21. 14-3-3 PROTEIN FUNCTION IN CELL GROWTH AND MOTILITY
    ANTHONY MUSLIN; Fiscal Year: 2001
    ..The expectation is that the results of these experiments will establish the importance of the 14-3-3 signaling molecules in cell growth regulation and development. ..
  22. S Checkpoint Function in Human Fibroblasts
    William Kaufmann; Fiscal Year: 2004
    ..This project will define genetic components of the S checkpoint and elucidate signal transduction mechanisms that underlie S checkpoint response in diploid human fibroblasts. ..
  23. POSTRECEPTOR DYSREGULATION IN DEPRESSION
    Yogesh Dwivedi; Fiscal Year: 2004
    ..abstract_text> ..
  24. Development of Digital SNP Analysis in Cancer Detection
    Ie Ming Shih; Fiscal Year: 2005
    ..Thus, the encouraging results from this study will ensure the detection of AI in plasma a promising cancer research direction for further exploration. ..
  25. Effects of tumor lethal factor on Kaposi's Sarcoma
    NICHOLAS DUESBERY; Fiscal Year: 2005
    ..This approach can form the basis for the development of a Kaposi's sarcoma therapeutic for clinical applications. ..
  26. Overcoming DC defects in cancer patients by VEGF trap
    Jeffrey Sosman; Fiscal Year: 2005
    ..Thereby, the correlative studies described here may lead to the establishment of VEGF inhibition, VEGF Trap, specifically, as an approach to combine with and enhance cancer immunotherapy. ..
  27. Epigenetic Chromatin Changes as Melanoma Markers
    Ruth Halaban; Fiscal Year: 2006
    ..Altogether, the results are likely to generate a novel marker(s) that can be used to assess propensity for malignant transformation, tumor progression and/or sensitivity to chemotherapeutic drugs that target chromatin conformation. ..
  28. A NEURAL TRANSCRIPTION FACTOR IN LUNG CANCER EVOLUTION
    Douglas Ball; Fiscal Year: 2006
    ..The proposed studies should provide novel insights in SCLC biology and a firm basis for determining whether hASH1, and hASHl-regulated growth mechanisms, should be intensively pursued as therapeutic targets for SCLC. ..
  29. Growth Factors and Colon Cancer
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..This study builds on a unique existing resource to study genetic and environmental associations with colorectal cancer. It will provide insight into colon cancer etiology and therefore avenues to disease prevention. ..
  30. Signal Transduction Mechanisms in Suicide Brain
    Yogesh Dwivedi; Fiscal Year: 2008
    ..abstract_text> ..
  31. A PROSPECTIVE STUDY OF ALASKA NATIVES & AMERICAN INDIANS
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..The AIAN cohort will serve as a resource to enhance research and training activities of AIAN students interested in health research, health education, and general public health. ..
  32. RGS PROTEIN FUNCTION IN CARDIAC PHYSIOLOGY
    ANTHONY MUSLIN; Fiscal Year: 2008
    ..These experiments will help define the role of RGS proteins in the pathogenesis of cardiac hypertrophy and contractile dysfunction and may provide important information for the development of novel therapeutic agents. ..
  33. Profiles of Sucsceptibility to Toxicant Stress
    William Kaufmann; Fiscal Year: 2007
    ..The UNC-CH toxicogenomics research program has the scientific expertise and organizational infrastructure to provide significant and substantial benefits to the Toxicogenomics Research Consortium. ..
  34. Prognostic Markers for Juvenile Pilocytic Astrocytomas
    Kwong Kwok Wong; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  35. 2003 Conference Pan-American Society Pigment Cell Resea
    Ruth Halaban; Fiscal Year: 2003
    ..3. To provide partial support to students and junior faculty to attend the meeting. They request funds for the 2003 meeting as well as for the 2 subsequent PASPCR annual meetings in years 2004 and 2006. ..
  36. FOUR-CORNERS BREAST AND ENDOMETRIAL CANCER STUDY
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2003
    ..C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated with respect to breast and endometrial cancer in a subset of women. ..
  37. PROLIFERATION & MALIGNANT TRANSFORMATION OF MELANOCYTES
    Ruth Halaban; Fiscal Year: 2004
    ..Our functional studies may provide a basis for the design of new therapeutical agents for the treatment of patients with metastatic melanomas. ..
  38. DIET AND SOMATIC MUTATIONS IN COLON CANCER
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2007
    ..e. p53, K-ras, and microsatellite instability). Differences in colon and rectal tumors will be compared. Additionally data from rectal tumors will be combined with that from colon tumors to define disease pathways. ..
  39. Mechanisms of Growth Inhibition by Helicobacter Pylor
    Hassan Ashktorab; Fiscal Year: 2003
    ..These studies will help to establish how bacteria can increase apoptosis possibly through generation of ROS and in specific circumstances this may alter one's risk of developing cancer. ..
  40. Paracrine IGF/GFBP Interactions In Vivo
    James Fagin; Fiscal Year: 2007
    ..abstract_text> ..
  41. METHYLATION PROFILING AND RISK OF COLORECTAL CANCER
    Hassan Ashktorab; Fiscal Year: 2007
    ..These studies will help in the detection and _rofiling of genetic changes in the pathway of CRC in AA. ..
  42. Inhibition of nf-kb signaling in melanoma therapy
    Jeffrey Sosman; Fiscal Year: 2005
    ..Abstract Not Provided ..